What are the treatment options for premature ejaculation?

Treatment of Premature Ejaculation

Premature ejaculation should be treated with daily selective serotonin reuptake inhibitors (SSRIs), on-demand clomipramine or dapoxetine (where available), or topical penile anesthetics as first-line pharmacologic therapy, with the strongest evidence supporting daily paroxetine for maximal ejaculatory delay. 1

Initial Assessment and Comorbidity Management

Before initiating treatment, obtain a detailed sexual history focusing on:

• Time to ejaculation (most important feature)
• Frequency and duration of PE
• Relationship to specific partners
• Impact on sexual activity and quality of life
• Presence of concomitant erectile dysfunction 1

If erectile dysfunction coexists with PE, treat the ED first, as PE may improve when ED is effectively managed. 1 Many patients with ED develop secondary PE due to anxiety or need for intense stimulation to maintain erection 1.

First-Line Pharmacologic Treatment Options

Daily SSRI Therapy (Strongest Evidence)

Daily paroxetine provides the greatest ejaculatory delay, increasing ejaculatory latency time (ELT) by a mean of 8.8-fold over baseline. 1

Recommended daily dosing regimens:

• Paroxetine: 10-40 mg/day (strongest efficacy) 1
• Sertraline: 25-200 mg/day 1
• Fluoxetine: 5-20 mg/day 1
• Citalopram: 20-40 mg/day 1
• Clomipramine: 12.5-50 mg/day (tricyclic antidepressant, more side effects than SSRIs) 1

The 2022 AUA/SMSNA guideline provides a Strong Recommendation (Evidence Level Grade B) for daily SSRIs as first-line agents 1. These medications have been shown to provide significant benefit over placebo in clinical trials 1.

On-Demand SSRI Therapy

On-demand dosing 3-6 hours before intercourse is modestly efficacious but provides substantially less ejaculatory delay than daily treatment:

• Paroxetine: 20 mg, 3-4 hours pre-intercourse 1
• Sertraline: 50 mg, 4-8 hours pre-intercourse 1
• Clomipramine: 25 mg, 4-24 hours pre-intercourse 1

On-demand treatment may be combined with initial daily treatment or concomitant low-dose daily treatment 1.

Topical Anesthetics

Lidocaine/prilocaine cream (EMLA cream): 2.5%/2.5%, applied 20-30 minutes pre-intercourse 1

Topical anesthetics are recommended as first-line agents alongside SSRIs 1. They provide drug-free spontaneity without systemic side effects 2.

Important Safety Considerations

SSRI-Related Adverse Effects

Common side effects from sertraline (representative of SSRI class):

• Ejaculation failure/delayed ejaculation: 11-14% (vs. 1% placebo) 3
• Decreased libido: 6% (vs. 1% placebo) 3
• Nausea: 25% (vs. 11% placebo) 3
• Insomnia: 21% (vs. 11% placebo) 3
• Dry mouth: 14% (vs. 8% placebo) 3

Critical Warnings

• Avoid SSRIs in men with bipolar depression due to risk of mania 1
• Serotonin syndrome risk with multiple serotonergic drugs (symptoms: clonus, tremor, hyperreflexia, agitation, fever; treatment: cessation of agents, benzodiazepines for symptom management) 1
• Caution in adolescents and men with comorbid depression regarding suicidal ideation, though elevated risk has not been found in non-depressed men with PE 1
• None of these medications are FDA-approved for PE; all represent off-label use with dosing regimens that may deviate from approved indications 1

Second-Line and Adjunctive Options

Alpha-1 Adrenoceptor Antagonists

Clinicians may consider α1-adrenoceptor antagonists for men who have failed first-line therapy, though efficacy data remains very limited and additional controlled studies are needed 1.

Combination Therapy

Combining behavioral and pharmacological approaches is more effective than either modality alone (Moderate Recommendation, Evidence Level Grade B). 1 Behavioral therapy leads to significantly greater increase in ELT compared to pharmacological therapy alone, with greater improvement in validated PE assessment scores 1.

Behavioral strategies include:

• Stop-start technique
• Squeeze technique
• Sensate focus exercises 4, 5

Evidence shows physical behavioral techniques improve IELT by 7-9 minutes over waitlist control in some studies, though results are mixed 5. Combined behavioral and drug treatment shows small but significant IELT improvements (0.5-1 minute) over drug treatment alone with better sexual satisfaction and ejaculatory control 5.

Treatments to Avoid

Surgical management (including injection of bulking agents, selective dorsal nerve neurotomy, pulsed radiofrequency ablation, hyaluronic acid gel augmentation) should be considered experimental and only used in ethical board-approved clinical trials. 1 Invasive treatments may cause permanent loss of penile sensation, and procedures like neurectomy and penile prosthesis implantation have risks that far outweigh benefits 1.

Treatment Goals and Patient Counseling

Patient and partner satisfaction is the primary target outcome for PE treatment. 1 Reassure patients that PE is a common and treatable disorder 1. Safety should be a primary consideration since PE is not life-threatening 1.

Discuss risks and benefits of all treatment options before intervention, including the off-label nature of pharmacologic therapies 1. Approximately 40% of patients either refuse to begin or discontinue SSRI treatment within 12 months due to concerns about taking antidepressants 1.

Clinical Algorithm

1. Obtain detailed sexual history; rule out/treat ED first if present 1
2. Initiate daily paroxetine 10-40 mg (strongest evidence) OR alternative daily SSRI OR topical anesthetic 1
3. Consider adding behavioral therapy for enhanced efficacy 1
4. If daily SSRI not tolerated or preferred, trial on-demand clomipramine or SSRI 1
5. If first-line therapy fails, consider α1-adrenoceptor antagonist 1
6. Avoid surgical interventions outside clinical trials 1